Present status of Catharanthus roseus monoterpenoid indole alkaloids engineering in homo- and hetero-logous systems.

Catharanthus roseus synthesizes one of the most structurally, chemically and biologically active phytomolecules monoterpenoids indole alkaloids (MIAs) with having a wide range of pharmaceutical activities. Being the sole source of antineoplastic MIAs vinblastine and vincristine C. roseus has become one of the most valued plant. The low in planta availability of these MIAs and unavailability of alternative chemical synthesis system has enhanced their demand and equally let to the exorbitant market cost. To bridge this gap alternative production systems have been investigated using MIAs metabolic engineering (ME) in the homologous and heterologous systems. The availability of improved recombinant technologies along with genomics and metabolomics tools has opened the door of tremendous new potentials of ME. To encash these potentials of ME for MIAs pathway, efforts were made by expressing constitutive structure biosynthesis enzymes, transporters, and transcription factors of C. roseus MIAs biosynthesis in both homologous and heterologous systems. Here we review the knowledge of C. roseus MIAs pathway metabolic engineering in homologous and heterologous systems, gained in the past 35 years of C. roseus research.

Anti-hemolytic, hemagglutination inhibition and bacterial membrane disruptive properties of selected herbal extracts attenuate virulence of Carbapenem Resistant Escherichia coli.

Expression of a multitude of virulence factors by multi-drug resistant microbial strains, e.g., Carbapenem Resistant Escherichia coli (Family: Enterobacteriaceae; Class: Gammaproteobacteria), is responsible for resistance against beta-lactam antibiotics. Hemolysin production and induction of hemagglutination by bacterial surface receptors inflicts direct cytotoxicity by destroying host phagocytic and epithelial cells. We have previously reported that Berberis aristata, Camellia sinensis, Cyperus rotundus Holarrhena antidysenterica and Andrographis paniculata are promising herbal leads for targeting Carbapenem resistant Escherichia coli. These herbal leads were analyzed for their anti-hemolytic potential by employing spectrophotometric assay of hemoglobin liberation. Anti-hemagglutination potential of the extracts was assessed by employing qualitative assay of visible RBC aggregate formation. Camellia sinensis (PTRC-31911-A) exhibited anti-hemolytic potential of 73.97 ± 0.03%, followed by Holarrhena antidysenterica (PTRC-8111-A) i.e., 68.32 ± 0.05%, Berberis aristata (PTRC-2111-A) i.e., 60.26 ± 0.05% and Cyperus rotundus (PTRC-31811-A) i.e., 53.76 ± 0.03%. Comprehensive, visual analysis of hemagglutination inhibition revealed that only Berberis aristata (PTRC-2111-A) and Camellia sinensis (PTRC-31911-A) exhibited anti-hemagglutination activity. However, Andrographis paniculata (PTRC-11611-A) exhibited none of the inhibitory activities. Furthermore, the pair wise correlation analysis of the tested activities with quantitative phytochemical descriptors revealed that an increased content of alkaloid; flavonoids; polyphenols, and decreased content of saponins supported both the activities. Additionally, flow cytometry revealed that cell membrane structures of CRE were damaged by extracts of Berberis aristata (PTRC-2111-A) and Camellia sinensis (PTRC-31911-A) at their respective Minimum Inhibitory Concentrations, thereby confirming noteworthy antibacterial potential of both these extracts targeting bacterial membrane; hemolysin and bacterial hemagglutination.

Attenuation of adhesion, quorum sensing and biofilm mediated virulence of carbapenem resistant Escherichia coli by selected natural plant products.

The multi-drug resistance offered by Carbapenem Resistant Escherichia coli (Family: Enterobacteriaceae; Class: Gammaproteobacteria) against third line antibiotics can be attributed towards its ability to develop biofilm. Such process involves adhesion and quorum-sensing induced colonization leading to biomass development. The present study explored the anti-adhesion, anti-quorum sensing and anti-biofilm potential of 05 pre-standardized potent herbals. Berberis aristata (PTRC-2111-A) exhibited maximum potential in all these activities i.e. 91.3% ± 0.05% (Anti-adhesion), 96.06% ± 0.05% (Anti-Quorum sensing) and 51.3% ± 0.07% (Anti-Biofilm formation) respectively. Camellia sinensis (PTRC-31911-A) showed both anti-adhesion (84.1% ± 0.03%) and anti-quorum sensing (90.0%) potential while Holarrhena antidysenterica (PTRC-8111-A) showed only anti-quorum sensing potential as compared to standards/antibiotics. These findings were in line with the molecular docking analysis of phytoligands against Lux S and Pilin receptors. Furthermore, the pairwise correlation analysis of the tested activities with qualitative, quantitative and bioactivity functional descriptors revealed that an increased content of alkaloid, moderate content of flavonoids and decreased content of tannins supported all the three activities. In addition, nitric oxide and superoxide scavenging activity were found to be correlated with anti-quorum sensing activity. The findings indicated clearly that B. aristata (Family: Berberidaceae) and C. sinensis (Family: Theaceae) were potent herbal leads with significant therapeutic potential which further needs to be explored at pre-clinical level in the future.

Effect of Holarrhena antidysentrica (Ha) and Andrographis paniculata (Ap) on the biofilm formation and cell membrane integrity of opportunistic pathogen Salmonella typhimurium.

Increasing occurrence of gastroenteritis outbreaks caused by food borne opportunistic microorganisms has become a major problem in food industry as well as in immunocompromised host. Antimicrobial agents are losing their efficacy due to increase in the microbial resistance. For such reasons, conventional treatment has become limited to manage the infections state. Need of the hour is to instigate the search for safer holistic alternatives. The present study was hence conducted to assess the antibiofilm effect and mode of action of aquo alcoholic extracts of Holarrhena antidysentrica (Ha) and Andrographis paniculata (Ap) against the Salmonella enterica serovar typhimurium. Both the extracts were screened for the presence of phytocompounds followed by the characterization using Attenuated Total Reflection (ATR) infrared spectroscopy and bioactivity finger print analysis. Anti-biofilm assays were determined to test the potential of both extracts to inhibit the biofilm formation, while Propidium Iodide (PI) uptake analysis revealed that cell membrane was damaged by the exposure of nutraceuticals for 1 h. This study has demonstrated that both nutraceuticals have anti-biofilm and antimicrobial activity perturbing the membrane integrity of food-borne S. typhimurium and could be used as curative remedy to control the food borne microbial infection.

Accumulation of reactivity to MBP sensitizes TRAIL mediated oligodendrocyte apoptosis in adult sub cortical white matter in a model for human multiple sclerosis.

Reactivity to myelin associated proteins is the hallmark of human multiple sclerosis (M.S) and its experimental counterparts. However, the nature of such reactivity has not been described fully. Herein, we report that myelin basic protein (MBP) reactivity accumulates in a rat model for M.S. over a period of time and sensitizes TRAIL mediated progressive oligodendrocyte apoptosis. We used active immunization by Myelin Oligodendrocyte Glycoprotein (MOG, 50 µg) to study chronic remitting relapsing encephalomyelitis in rats. A time point analysis of the progressive disease revealed cumulative accumulation of anti myelin basic protein antibodies during the disease progression with minimal change in the anti-MOG antibodies. Increased reactivity to MBP was studied to sensitize TNF related apoptosis-inducing ligand (TRAIL) and other proinflammatory cytokines in a cumulative fashion leading to the Caspase dependent apoptosis of oligodendrocytes and myelin loss. In a rescue experiment, we could limit the demyelination and prevent disease progression by neutralizing the effector, TRAIL in an early stage of the disease. This is the first study to identify the accumulation of MBP antibodies in MOG induced EAE which possibly leads to TRAIL sensitized oligodendrocyte apoptosis in the white mater of EAE rats. This finding stresses on the need to study MBP antibody titers in M.S. patients and therefore might serve as an alternate marker for progressive demyelination.

Camellia sinensis Ameliorates the Efficacy of Last Line Antibiotics Against Carbapenem Resistant Escherichia coli.

Aquo-ethanolic extract of Camellia sinensis (PTRC-31911-A), standardized using Fourier transform infrared analysis, was found to have seven common functional groups in comparison with pre-identified marker compound 'quercetin'. Phyto-chemical quantitation analysis revealed the presence of 10.65 µg/mg of flavonoids. The bioactivity fingerprint profile of PTRC-31911-A includes IC50 (Hydroxyl radical site specific scavenging) = 11.36 ± 0.5 µg/mL, IC80 (Hydroxyl radical non-site specific scavenging) = 26.44 ± 0.5 µg/mL and IC50 (Superoxide ion scavenging) = 10.141 ± 0.5 µg/mL. The drug combination analysis of PTRC-31911-A with five third-line antibiotics was carried out against carbapenem-resistant Escherichia coli. The analysis of combination of PTRC-31911-A (6.25-1000 µg/mL) and antibiotics (6.25-1000 µg/mL) revealed synergistic behaviour (fractional inhibitory concentration indices < 1) with tigecycline, ertapenem, meropenem, colistin and augmentin. The lead combination of PTRC-31911-A + ertapenem or meropenem showed maximum augmentative potential at 50 and 100 µg/mL, respectively, with nearly five-fold decrease in minimum inhibitory concentrations as compared with respective antibiotics alone. The synergistic effects implied that the antibacterial combinations of PTRC-31911-A and ertapenem, meropenem, colistin, tigecycline or augmentin would be more effective than a single monotherapy with either of the antibacterial agent.

The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity.

The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against γ-radiation-induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy γ-irradiation (dose reduction factor = 1.27). The study revealed significant (p < 0.05) changes in levels of catalase (12.57 ± 2.58 to 30.24 ± 4.89 units), glutathione peroxidase (6.23 ± 2.95 to 13.26 ± 1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25 ± 5.6 to 11.65 ± 2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74 ± 0.2 to 16.09 ± 3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76 ± 0.41 × 10(6) to 9.25 ± 0.24 × 10(6) ), hemoglobin (2.15 ± 0.48g/dL to 14.77 ± 0.25g/dL), hematocrit (4.55 ± 0.24% to 37.22 ± 0.21%), and total leucocyte count (1.4 ± 0.15 × 10(6) to 8.31 ± 0.47 × 10(6) ) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2-1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation-induced decrease (p < 0.05) in regulatory T-cells (Tregs ) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 641-654, 2016.

A semiquinone glucoside derivative provides protection to male reproductive system of the mice against gamma radiation toxicity.

Present investigation was carried out to evaluate the radioprotective efficacy of a novel Semiquinone glucoside derivative (SQGD), isolated from Bacillus sp. INM-1, in the male reproductive system of BALB/c mice. Animals were administered 50 mg/kg b.wt. (i.p.) SQGD 2 h before whole body γ-irradiation (10 Gy). Radiation-induced cellular toxicity and its modulation by SQGD pretreatment was evaluated in the mice testes by quantitative histological and protein expression analysis. SQGD pretreatment protects irradiated mice from radiation-induced testicular atrophy and germ cells degeneration, which may lead to emptiness of seminiferous tubules. Significant decrease in P53 and P21((Cip/WAF-1)) expression was observed in the irradiated mice pretreated (2 h) by SQGD at 6 h compared with only irradiated mice. However, contrary to P53, expressions of P21 at latter time, that is, 24-72 h was found to be increased significantly in the irradiated mice pretreated by SQGD. Significant increase in the intact PARP-1 protein expression were observed in the testes of the mice pretreated by SQGD 2 h before irradiation at 24-72 h compared with the only irradiated mice, whereas significant increase in PARP-1 cleaved fragment was noticed at 24 h. Similarly, significant increase in NF-kB and BCL-2/BAX expressions ratio was noticed in SQGD-treated mice (± irradiation) compared with irradiated mice, suggested a role of SQGD in the activation of prosurvival signaling in the testicular germinal cells population of the irradiated mice and thus contributed to protection against lethal γ-irradiation.

Elucidation of the Role of TRPV1, VEGF-A, TXA2, Redox Homeostasis, and Inflammatory Cascades in Protection against Cold Injuries by Herbosomal-Loaded PEG-Poloxamer Topical Formulation.

High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level. The condition is exacerbated in individuals having inadequate and proper covering and layering, particularly when large area of the body are exposed to extremely cold environments. There is a paucity of preventive and therapeutic pharmacological modalities that have been explored for managing and treating cold injuries. Given this, an efficient modality that can potentiate the healing of frostbite was investigated by studying various complex pathophysiological changes that occur during severe cold injuries. In the current research, we report the effectiveness and healing properties of a standardized formulation, i.e., a herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF), on frostbite. The intricate mechanistic pathways modulated by the novel formulation have been elucidated by studying the pathophysiological sequelae that occur following severe cold exposures leading to frostbite. The results indicate that n-HPTF ameliorates the outcome of frostbite, as it activates positive sensory nerves widely distributed in the epidermis transient receptor potential vanilloid 1 (TRPV1), significantly (p < 0.05) upregulates cytokeratin-14, promotes angiogenesis (VEGF-A), prominently represses the expression of thromboxane formation (TXA2), and significantly (p < 0.05) restores levels of enzymatic (glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic antioxidants (glutathione). Additionally, n-HPTF attenuates oxidative stress and the expression of inflammatory proteins PGF-2α, NFκB-p65, TNF-α, IL-6, IL-1ß, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and protein carbonylation (PCO). Masson's Trichrome staining showed that n-HPTF stimulates cellular proliferation, and increases collagen fiber deposition, which significantly (p < 0.05) promotes the healing of frostbitten tissue, as compared to control. We conclude that protection against severe cold injuries by n-HPTF is mediated via modulation of pathways involving TRPV1, VEGF-A, TXA2, redox homeostasis, and inflammatory cascades. The study is likely to have widespread implications for the prophylaxis and management of moderate-to-severe frostbite conditions.

Treatment Outcome of Drug-Resistant Skeletal Tuberculosis: A Retrospective Analysis.

Background: Management outcomes of drug-resistant (DR) osteoarticular tuberculosis (OATB) is dismal as in pre-ATT era (1905). The studies documenting treatment outcome of DR-OATB are scarce; hence, present retrospective analysis was conducted to evaluate outcome of consecutive cases of DR-OATB. Methods: 45 consecutive patients of suspected DR-OATB were treated from 2010 onwards. Tissue samples were submitted for AFB smear, cytology/histology, liquid culture, CBNAAT/LPA besides gram's staining and aerobic/anaerobic culture. Patients were treated by individualized second-line ATT till documenting healed status by contrast MRI/PET. The changes in neurological deficit, deformities, and drug-induced adverse events were documented. Results: 37/45 patients, 15 males and 22 females, mean age 26.89 years were followed. DR was suspected observing poor clinico-radiological response/appearance of fresh lesions on ATT. All showed no growth on aerobic/anaerobic pyogenic culture. 29 (78%) had microbiologically proven drug resistance and 8 (22%) were labeled as clinical drug resistance (CDR). 18/29 had multi-drug resistance. Mean prior ATT intake was 12.03 months 15 (40%) underwent surgical decompression. Mean duration of second-line ATT was 22.5 months (9-36 months). All patients achieved healed status with 8 (21%) developed side effects, most commonly hepatotoxicity, ototoxicity, and psychiatric disturbances. Average follow-up after completion of ATT was 40.5 months. Conclusion: We report a large series where patients of DR-OATB were suspected on clinical criteria, investigated by DST, and treated. Patients with proven drug resistance were treated by individualized second-line ATT. CDR cases were treated by MDR protocol. Genotypic DST (CBNAAT/LPA) improved demonstration of DR. We demonstrated healed status on MRI/PET with no recurrence at minimum 2-year follow-up.

Cervicodorsal spine tuberculosis-- surgical approach.

Background: Tuberculosis (TB) of CT junction is uncommon (5 % of all spinal TB), and difficult to approach surgically in view of its deep location with sternum in front and scapula in the back. We present 7 consecutively treated cases of cervico-thoraccic TB for outcome of treatment and discuss rationale of choosing surgical approach. Methods: Present study includes 7 freshly diagnosed cases of CT junction TB. Plain radiographs, sagittal reconstruction of CT spine that included sternum on CT/MRI was performed in all cases. Disc space below the distal healthy vertebrae was identified and a line parallel to disc space was drawn. If this line passes above suprasternal notch, it was inferred that this VB can be accessed by anterior cervical approach. If disease focus was at or below suprasternal notch level, manubriotomy/sternotomy was added for better visualization of the lesion. Results: All seven cases were female, with mean age of 20 years (9-45 years). The vertebral lesion involved 2VB (n = 3), 3VB (n = 2) and >3 VB (n = 2). The average Cervico-thoracic kyphosis was 15° (range 10-25°). All 7 cases were operated for anterior decompression, kyphotic deformity correction and instrumented stabilization. Anterior cervical approach and manubriotomy/sternotomy approach was performed in three cases each. In two pan-vertebral cases we performed 360° procedure. Six cases have shown first sign of neural recovery within 3 weeks of surgery and almost complete neural recovery at 3 months follow-up while one case showed partial recovery. ATT was stopped after 12 months once healed stage was demonstrated on contrast MRI in all. Conclusions: CT junction TB usually presents with severe kyphotic deformity/neural deficit. These cases require anterior decompression/corpectomy, deformity correction, gap grafting and instrumented stabilization with anterior cervical plate. Lesion with pan-vertebral disease is stabilized 360°. These lesions can be decompressed by lower anterior cervical approach with/without manubriotomy. The Karikari method was useful in deciding the need for manubriotomy to decompress the lesion.

Tubercular Osteomyelitis of Navicular Bone: A Rare Site for Bone Tuberculosis.

Introduction: Tuberculosis (TB) is a global public health problem, endemic to India. Osteoarticular TB uncommonly presents in the foot, navicular osteomyelitis is an extremely rare entity. Case Report: We report a rare case of navicular osteomyelitis caused by TB in a 37-year-old man who presented to OPD with swelling and dull aching pain over the dorsum of his left foot. A radiograph of the foot showed a lytic lesion in the navicular bone. Further investigations in the form of aspiration cytology, cartridge-based nucleic acid amplification test, and acid-fast bacilli culture confirmed TB. Category-1 anti-tubercular therapy was started immediately and the patient was treated conservatively. Four drugs (HRZE) were given for 2 months and 3 drugs (HRE) for 9 months, after which the patient stopped his medications on his own. Radiographs and CEMRI at 14-month follow-up showed a healed lesion. Conclusion: This case illustrates an exceptional location of osteoarticular TB and shows that Navicular TB can be treated conservatively with near-complete function and recovery if diagnosed early.

Dietary agents in the prevention of radiation-induced nausea and vomiting (RINV): review addressing the scientific observations, benefits, lacunae and future direction.

PURPOSE: Radiation-induced Nausea and Vomiting (RINV) is an important side effect and conservative estimates are that 50-80% of the patients undergoing curative radiotherapy (RT) will experience some sought of retching, nausea, and/or vomiting during the course of their treatment. Conventionally, antiemetic drugs like the 5-hydroxytryptamine receptor antagonists and steroids are the mainstay of treatment. However, the use of these agents, especially steroids, can cause side effects and thereby negate the proposed benefits. The antiemetic effects of Centella asiatica (Indian pennywort), Hippophae rhamnoides (Sea buckthorn), oil of Mentha spicata (Spearmint) and the rhizomes of Zingiber officinale (ginger) have been addressed. CONCLUSIONS: Results indicate that Indian pennywort, Sea buckthorn, Spearmint oil and ginger are beneficial in mitigating RINV. Also, of the four plants investigated in preclinical models of study, mint oil and ginger seem to be more useful and merit structured systematic translational studies to ascertain the benefit of these two agents.

Ocimum sanctum L (Holy Basil or Tulsi) and its phytochemicals in the prevention and treatment of cancer.

Ocimum sanctum L. or Ocimum tenuiflorum L, commonly known as the Holy Basil in English or Tulsi in the various Indian languages, is a important medicinal plant in the various traditional and folk systems of medicine in Southeast Asia. Scientific studies have shown it to possess antiinflammatory, analgesic, antipyretic, antidiabetic, hepatoprotective, hypolipidemic, antistress, and immunomodulatory activities. Preclinical studies have also shown that Tulsi and some of its phytochemicals eugenol, rosmarinic acid, apigenin, myretenal, luteolin, ß-sitosterol, and carnosic acid prevented chemical-induced skin, liver, oral, and lung cancers and to mediate these effects by increasing the antioxidant activity, altering the gene expressions, inducing apoptosis, and inhibiting angiogenesis and metastasis. The aqueous extract of Tulsi and its flavanoids, orintin, and vicenin are shown to protect mice against γ-radiation-induced sickness and mortality and to selectively protect the normal tissues against the tumoricidal effects of radiation. The other important phytochemicals like eugenol, rosmarinic acid, apigenin, and carnosic acid are also shown to prevent radiation-induced DNA damage. This review summarizes the results related to the chemopreventive and radioprotective properties of Tulsi and also emphasizes aspects that warrant future research to establish its activity and utility in cancer prevention and treatment.

Ginger in the prevention of nausea and vomiting: a review.

Nausea and vomiting are physiological processes experienced by every human being at some stage of their life. They are complex protective mechanisms and the symptoms are influenced by the emetogenic response and stimuli. However, when these symptoms recur frequently, they can significantly reduce the quality of life and can also be detrimental to health. The existing antiemetic agents are ineffective against certain stimuli, are expensive, and possess side effects. Herbal medicines have been shown to be effective antiemetics, and among the various plants studied, the rhizome of Zingiber officinale, commonly known as ginger, has been used as a broad-spectrum antiemetic in the various traditional systems of medicine for over 2000 years. Various preclinical and clinical studies have shown ginger to possess antiemetic effects against different emetogenic stimuli. However, conflicting reports especially in the prevention of chemotherapy-induced nausea and vomiting and motion sickness prevent us from drawing any firm conclusion. The current review for the first time summarizes the results. An attempt is also made to address the lacunae in these published studies and emphasize aspects that need further investigations for it to be of use in clinics in the future.

Top 50 Cited Papers on Tibial Plateau Fracture Management: A Bibliometric Analysis and Review.

Purpose: The orthopaedic surgeons, especially the young budding surgeons should have a well-balanced knowledge of the past evidence as well the current evidence in the literature for the appropriate as well as optimum management of tibial plateau fractures. Bibliometric analysis of the top-cited papers on tibial plateau fracture management can help know their concurrent interests, deficiencies and conflicting issues regarding their management. This study aimed to identify the 50 most cited research articles in tibial plateau research and analyse their characteristics. Methods: We searched the Thompson Reuters Web of Science database for articles relevant to tibial plateau fracture and prepared a list of top 50 cited articles that included original articles and review articles concerning tibial plateau fractures. The included articles were analysed for contributing journals, corresponding author's country, publication year, cumulative citations, annual citations, citation trends over time, level of evidence and a qualitative review. Results: The search strategy resulted in 2263 articles. The top 50 cited articles were published from 1974 to 2014 and belonged to 12 journal sources. There were 47 original articles and 3 review articles. The average citations per article were 126.2, and the annual citations per article were 6.478 per year. The top-cited articles were relevant to the strategies in the management, classification, fracture reduction, articular restoration, types and number of fixation devices, surgical approaches, associated menisco-ligamentous injuries and applicability of bone grafts/substitutes in tibial plateau fractures. Conclusion: The current bibliometric analysis summarises the top-cited evidence concerning tibial plateau fractures and can be a potential resource for reviewing and locating the same. The analysis shows that most top-cited evidence belongs to the year 2000 onwards. Also, recent articles have a higher annual citation rate. A limited number of journals and mostly, western countries have contributed to the top-cited evidence. Whilst the top-cited evidence has touched several aspects of tibial plateau fractures, it is in the form of level IV case series. It needs better prospective evidence to establish sound recommendations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-00932-4.

Effect of COVID-19 on the Burden and Profile of Orthopaedic Patients Admitted Post-Resumption of Routine Services in a Tertiary Care Hospital in Delhi.

Purpose On resumption of routine services post-lockdown during coronavirus disease 2019 (COVID-19), we expected a backlog of orthopaedic patients who could not get appropriate and timely care and would now present with complications due to missed or delayed treatment. This study aimed to quantify the effect of COVID-19 on the burden and profile of orthopaedic patients admitted post-resumption of routine services. Materials and methods Data on all the patients admitted to the orthopaedic department were collected using an interviewer-administered schedule for a complete one-year period after the resumption of routine orthopaedic services in a tertiary care hospital in Delhi. For comparison of the burden of trauma patients with that during the pre-COVID-19 period, data were obtained from a similar study done on trauma patients in 2017 at the same institution. For patients with non-traumatic conditions, previous hospital records were used. Results A total of 1585 patients were admitted during the one-year period post-resumption of routine services following COVID-19 restrictions, which was 41% less than that compared to the corresponding pre-COVID-19 data. The proportion of patients from other neighbouring states showed a decline from 52% in the pre-COVID-19 period to 41.55% when healthcare services resumed during the COVID-19 period. Out of all admitted trauma patients in 2021, 12.7% presented with a missed or complication of treatment as compared to 3.1% in the pre-COVID period. Around half of them (52.5%) attributed their complications to a COVID-19-related lockdown. Conclusion There was a significant decline in the number of patients post-resumption of routine orthopaedic care services. Converting whole tertiary care teaching hospitals to COVID-19-dedicated hospitals must not be done as it leads to an increase in missed or complication of orthopaedic treatment.

Radioprotection to small intestine of the mice against ionizing radiation by semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1.

Ionizing irradiation induces severe damage to the intestinal crypt cells which are responsible for renovation and maintenance of the intestinal cellular architecture. Therefore, protection of intestinal cells and tissue against lethal irradiation using a semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 is the prime focus of the present investigation. BALB/c mice were administered by SQGD (50 mg/kg.b.wt. i.p.) 2 h before whole body irradiation (10 Gy), and histological analysis of the jejunum section was carried out and compared to the irradiated mice. Significant (p < 0.0001) increase in villus length, number of cells per villus, crypts numbers per villus section, total cells counts and mitotic cell counts per crypt and low goblet cells per villus section, and low apoptotic index per crypt section were observed in the irradiated mice pre-treated by SQGD at 48-168 h. Significant induction in NF-kß at 24 h and Bcl-2/Bax ratio was observed in irradiated mice pre-treated by SQGD compared to only irradiated animals. SQGD pre-treatment before irradiation was found instrumental to reverse the radiation-induced degenerative changes by replenishment of the damaged cells by enhancing mitotic, proliferating, pro-survival, and apoptosis inhibitory activities probably through modulation of cell cycle arrest in G(1)/S phase in the intestinal cellular milieu.

Design and optimization of a novel herbosomal-loaded PEG-poloxamer topical formulation for the treatment of cold injuries: a quality-by-design approach.

The spectrum of cold injuries ranges from frostnip, chilblains to severe frostbite. Cold injuries occur upon prolonged exposure to freezing temperature and are pathologically a combination of ice crystal formation in the tissue resulting in inflammation, thrombosis and ischemia in the extremities, often necessitating limb amputation in extreme cases due to tissue necrosis. Severe forms of frostbite are a cause of major concern to patients as well as the treating physician. Due to the lack of effective treatment modalities and paucity of research on prophylaxis and therapeutics of cold injuries, we developed a novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) employing quality-by-design (QBD) approach. Natural compounds exhibiting potent therapeutic potential for the management of cold injuries were incorporated in novel lipid vesicles (herbosomes) loaded in PEG-poloxamer polymers. The herbosomal formulation effectively creates an occlusion barrier that promotes epithelial regeneration, desmosome scale-up and angiogenesis and thus promotes rapid healing, indicating controlled release of herbosomes. Optimized novel herbosomes showed entrapment efficiency > 90% and < 300 nm mean particle size and in vitro drug permeation of about 2 µg/cm2 followed Higuchi's release kinetics. Skin irritancy study on female Sprague-Dawley rats showed no edema or erythema. In vivo bio-efficacy study revealed significant efficacy (p < 0.05) when compared to the standard treatment groups. Graphical abstract presenting the designing and optimization of novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) and predictive model for the in vivo study of the developed n-HPTF on cold injury rat skin model.

Effect of Tunnel Drilling Portal on Femoral Tunnel Entry Aperture's Location in Arthroscopic Anterior Cruciate Ligament Reconstruction.

Introduction Transportal techniques for femoral tunnel drilling have the advantage of anatomical anterior cruciate ligament reconstruction, which was earlier difficult to achieve through transtibial femoral tunnels. However, the medial arthroscopic portal used for femoral tunnel drilling in single-bundle anterior cruciate ligament reconstruction (ACLR) has not been uniformly placed in different studies. Therefore, we performed a computed tomography-based analysis to compare the femoral tunnel entry aperture of the ACLR cases that used the standard AM portal and those using a far medial portal for femoral tunnel drilling. Methods We retrospectively reviewed computed tomography images of patients who underwent isolated single-bundle ACLR in our institute with either standard anteromedial portal or the far medial portal used for the femoral tunnel drilling. The femoral tunnel aperture's depth and height, measured using the quadrant method, were compared between the two portal methods. Results A total of forty-two case records were reviewed, sixteen belonging to standard anteromedial portal technique and twenty-six belonging to far medial portal technique. The tunnels created through the far AM portal were significantly shallower (more anterior) and inferior than the standard AM portal-created femoral tunnels. Conclusion The choice of drilling portals can influence transportal femoral tunnel drilling. A tendency towards anterior and inferior positioning of the femoral tunnel entry aperture has been observed when a far medial arthroscopic portal is used for femoral tunnel drilling. Therefore, care must be taken to ensure that the drilling guide pin position does not change when the reamer is passed over it.